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How can non-contributing agenciesbe encouraged to participate
Kristin Raudsepp, MDDirector General,
Estonian State Agency of MedicinesHMA Management Group
HMA Resource Planning Working Group
Estonia
Population: 1,34 mill(65% Estonians)
The presentation• What do we mean with “contributing agency”• What do we mean with “co-operative company”• Why do they do it• What can be done to encourage wider
participation?• Situation with different procedures• Update of the medicinal products market in
Estonia.
Some useful links• http://www.hma.eu
What is new agency• 1957: 6 countries in EU• 1973: 3 new countries in EU• 1981: 1 new country in EU• 1986: 2 new countries in EU• 1995: 3 new countries in EU• 2004: 10 new countries in EU• 2007: 2 new countries in EU• 20.....
EU procedures needing resources from MS
• monographs for HMPC• COMP• EC working groups
• coordinators for PMF Certification
• (co)rapporteurs (incl MRL) at the CVMP
• CHMP peer review appointments
• (co)rapporteurs at the CHMP
• CMDv - Decentralised new applications
• CMDv - Mutual recognition new applications
• CMDh - Decentralised new applications
• CMDh - Mutual recognition new applications
• (co) rapporteurs for scientific advice referred to the WP by the CHMP Scientific Advice WP
• (co)rapporteurs for dossier evaluation referred to the WP
• (co)rapporteurs for concept papers/guidelines/documents for CHMP WP-s
2
2007 EU new applications• New applications MRP started - 396• New applications DCP started - 1033• The total number of new applications for
initial evaluation in CHMP - 90
No of Selected Activities in the EU network in 2006
(*the numbers may differ because of the variety of sources)
0
50
100
150
200
DE NL UK SE DK FI FR ES IE IT BE PT NO HU CZ EE SI AT LU PL LT IC MT SK GR LV CY LI
HMPC, No of monographs, active in 2006
CVMP, No of (co)rapporteurships (incl MRL), active in Dec 2006
CMDv - Decentralised new applications finalised in 2006
CMDv - Mutual recognition new applications finalised in 2006
CMDh - Decentralised new applications finalised in 2006
CMDh - Mutual recognition new applications finalised in 2006
CHMP, No of (co) rapporteurs for scientific advice referred to the WP by the CHMP SA WP
CHMP, No of (co)rapporteurs for dossier evaluation referred to the WP, active in 2006
CHMP, No of (co)rapporteurs for concept papers/guidelines in WP-s, active in 2006
CHMP, No of peer review appointments in 2006
CHMP, No of (co)rapporteurships, new appointments in 2006
No of employees in CA of EEA + EMEAhuman+vet, and in some countries cosmetics, devices, reimb, pestic
HMA 2008
0
200
400
600
800
1000
1200
DE1
FR
1U
K1
DE2 DK
SE
ES
RO
1
BE
PT
PL
CZ
1
AT IE EL
NO
NL
HU FI
UK
2
BG
LV
RO
2
LT SI
CZ
2 EE DE
FR
2 ISS
K2 IT MT
CY
1C
Y2
LU
EMEA
Contributing agencies• Agencies with resources and motivation• Agencies with no resources, but with
motivation• (Agencies with resources, but with no
motivation)
• Estimated MRP/DCP procedures in MS range from 2 to 400 per year.
Possible view of a MS about motivation• Acting as a RMS or (co)rapporteur does not
often mean the product will be put on the market of the MS after the granting of marketing authorisation.
• Being active and working diligently in the European market processes, does not help small countries to get products on their own. State Agency of Medicines
ESTONIA;e-mail: [email protected];
homepage: www.ravimiamet.ee
3
What is our situation in Estonia
• The budget of SAM in 2008 is 2,5 million Euros which is 40 times less than budget of biggestCAs in EU
• We have 80 people (covering MA, druginformation, adverse reactions, inspections, lab, clinical trials, veterinary medicines, medicaldevices, biological products)
What have we done to cope• Priority list of targets and actions• Risk analyses• Learning from the more experienced
agencies• Quality system• Benchmarking• Perfomance indicators• Following the plan, but being flexible
The Estonian Medicinal Products Market
(billion EEK, wholesale data)
0,891,13
1,31,47 1,6
1,92 2,012,26
2,67
0
0,5
1
1,5
2
2,5
3
1999 2000 2001 2002 2003 2004 2005 2006 2007
+17,9%+12,4%
+4,8%
+20,4%
144,5 millionEUR
171millionEUR
Patients’ needs in small countries
Patients’ needs in small countries
• The same as in bigger and richer ones
Patients’ needs in small countries
• The same as in bigger and richer ones–i.e. Access to the medicineswhich efficacy, quality and safety has been proven and maintained through its cycle
4
The side effects of being small• Big opportunity to work as a fireman• The risks are high, as one individual is
responsible for too big part of your work• The limited number of good people• The same limited number of good people
is attractive for the companies
Estonia as a RMS(applications received)
• 2005 – 3 MRP• 2006 – 1 DCP• 2007 – 11 DCP + 2 MRP + 1 RU MRP• 2008 6k – 30 DCP• First MRP ended 30.06.2005
ketoconazole
Initial applications per type in Estonia
Initial applications 2004-2008 6 month
75 71 53 34 9
171
0
2056
24 3118
195
280 448 476
319
4
8
915
53
028
16
31 17
14
0
100
200
300
400
500
600
700
2004 2005 2006 2007 2008 6 month
Line extension
Hybrid
Fixed combination
Generic
Bibliographic
Informed concent
Full dossier
MA applications in Estonia
376 363 325 448 548 574 335186 355 458 456 396 279 180
19852974
3984
57567105 7323
2301
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
2002 2003 2004 2005 2006 2007 2008-6k
Variations
Renewal
Initial
Started procedures in EU
RMS for MA Applications (MRP/DCP) in 2008
0
5
10
15
20
25
30
35
40
AT BE BG CY CZ DE DK EE EL ES FI FR HU IE IS IT LI LT LU LV MT NL NO PL PT RO SE SI SK UK
Source: Feb07 to Jan08 CMD(h) Press Releases
Dilemmas of the agency• Do we trust each other enough to rely totally on
mutual recognition• How many centr assessments or RMS is enough• Workload has increased considerably because
of the broad range of topics (regulatory, procedural and scientific)
• Interest for fees• The agency does not have legal way to refuse
from EU work• The agency does not have legal pressure about
how much EU work should be done
5
Concerns of industry• Limited resources available in Member States to
be Rapporteus, to be RMS, to run the processefficiently, to meet timelines
• Delay in some phase of the assessment• Clock stop not very transparent- delays with
restart• Booking submission slots in advance• Re-assessment of the Application in parallel by
some CMS
The main criteria of the companies for selecting a RMS in MRP/DCP seem to be:
• Importance/size of the market within the (EU)• Ability of the RMS to defend the product against other
Concerned Member States (CMS)• Long-term partnership• Open to dialogue• Respecting time lines• Consideration of future variations• Expertise in respective medical field• Potential for specific up-front agreements• In DCP the size of the market and respecting time lines
criteria are not so important as the license will be granted at the same time for all the involved Member States.
MRP/DCP – is there any problem• The latest trends show that Applicants
aren’t free to choose the RMS• They have to take what is available• Most of the agencies are willing to act as a
RMS, but for several reasons the no of procedures per year is limited.
View of the Member State• To take the RMS
– feeling responsible for theEU market
– the work is interesting– trusting expertise only from
inside the country– motivation to be the part of
the game– keeping continuous
development of thepersonell
– enough free resources– everyday practice and
normal way of working– motivating fees
• Not to take the RMS– too new to understand the
game– too old to fight for heavy
workload– too small to attract the
product to our market afterwards
– too big to attract theproduct on our market anyway
– not enough experts– too much other works to do– non-motivating fees
How do the agencies handle the requests for RMS-ship?
• Some: All requests are accepted• Some: Depends on the type of the application• Some: Procedure starts immediatedly after validation• Booking system
– Number of procedures in queue range from just one to 725. Totally (all agencies together) almost 1800 procedures are in queue. The booking time limits reported range from 6 months to no time limit, most agencies have a time limit of 18-24 months.
• Most of the agencies would like to participate as RMS in DCP to a larger extent
• Some agencies have differences in approach, but most agencies have described built in flexibility
CHMP – criteria for choosing theRap/co-Rap
• CHMP Rapporteur/Co-Rapporteur Appointment: Principles, Objective Criteria and Methodology. London 12 July 2006, EMEA/124066/2005
• The procedure foresees, according to the new Pharmaceutical legislation, the criteria for Rapporteur appointment at the CHMP
• Different from the previous procedure:– the Applicant's proposals/preferences will not be considered for the appointment
of Rapporteur/Co-Rapporteur– the workload statistics play a minor role
• The appointment of Rapporteur/Co- Rapporteur and their assessment teams shall be made on the basis of objective criteria, which will ensure the provision of objective scientific opinions and will allow the use of the best and available expertise in the EEA in the relevant scientific area.
6
The criteria for choosing Rap/Co-Rap• Ability of Rapporteur/Co- Rapporteur to fulfil their role, which
refers mainly to their ability to take responsibility for the scientific assessment /evaluation undertaken by the assessment team, coordination input etc
• Assessment Team Objective Criteria which refer to the scientific competence, regulatory experience, complementary cross-team scientific expertise and competence of the Assessment Team(s) as well as the availability of an adequate Quality Assurance System at the level of the EEA NCAs
• Individual Objective Criteria which refer to the academic expertise and the direct working experience and competence of the– Individual assessor/expert – Rapporteur/Co-Rapporteur (when acting as assessor/expert in the
scientific assessment of the application)
Thoughts about the Rules• The timing to introduce this could not have been worse,
as it came exactly at the time where new MS-s would have been introduced as Rapporteurs/Co-Rapporteurs
• Instead of trying to equalize the work-load, the rules favour the already hard-working NCA-s and leave little chance to new Rapporteur/Co-Rapporteur
• In reality, the new MS-s have been appointed Co-Rapporteurs. This has been possible either due to– lack of interest of the old MS-s– pragmatic breach of rules by the secretariat and CHMP
chairman, as by definition the experience of new MS-s e.g. in EU regulatory affairs cannot compete with the old MS-s
– lots of available work
Thoughts about the Rules, II• The appointment procedure seems to be less transparent than the
old ‘statistics’ based system, as some of the the criteria, as listed above, are open to wide interpretation.
• This biases the system towards preference to bigger agencies, who can always list an A-team of highly experienced assessors, who will later have little to do with the actual assessment.
• Some agencies pick ‘scientifically interesting’ dossiers only, others take whatever is available and thirds hardly do anything.
Historical reasons, fixed centres of expertise
• The system is pretty focused on the experience of the CHMP member/NCA behind her/him – this does not allow ‘reformed agencies’ or new MS-s to participate fully in the procedures.
Centralised Procedure• Are there applications for which rapporteurs are
not found– The generic applications seem to draw little
competition, as well as fixed combinations of old products and, possibly, OTC-s
– Volunteers for SPC harmonisation referrals, re-examinations
• MSs interest for Fees– The rapp-ship bids are obviously dependent on fees.
It is harder to find workforce for unpaid jobs like referrals or peer review.
Proposals for better regulation of the situation in central procedures
• A system, more encouraging for new agencies, needs to be introduced in the interest of sustainability of the system.
• Incorporating these agencies into the CHMP work needs to be a formal goal. There is no excess of assessors at any of the agencies, not even the biggest. Any help needs to be used.
• The model for future needs to be that most of the agencies have regulatory competence and sustainable ’generalist’ assessment teams, as well as a functioning quality system. The agencies need to work routinely in the CP, be it 1-2 new product dossiers per year for a small agency. If the need for a specific competence arises, the European expert network and co-operation with other agenciesneeds to be able to provide it.
7
What the agencies do to solve theavailability problem of resources
• Serious effort to avoid public health problems• HMA strategic discussions on resources
– Ensuring that available resources are sufficient to support the work of the network.
– Common ideas to strengthen the EU Regulatory System network– Creation of trust and mutual understanding in the network
(Quality management systems, benchmarking)– Searching the ways to share resources between NCAs
• Competence development, top quality scientific expertise• National initiatives
Co-operative company• To be good on agency side and perform excellent you
must have good partners also - the good MA procedure starts with the receipt of high-quality application
• Constructive dialogue (pre-submission, during evaluation, post-authorisation)
• Keeping the deadlines and promises• Declears very clearly the contact point for the agency
(preferrably not the secretary)• Is able to give quickly explanations during technical
assessment• Doesn’t book parallel time slots.• Puts enough energy into the quality of translations of
product information
The dream The reality
Conclusion• Non-contribution has the reason and it is
not associated only with size of thecountry or years in EU
• New agencies in EU procedures meangood opportunity (additional experts and knowledge, the number of possible RMS has more than doubled)